How does impaired renal function affect the dosing of apixaban (Eliquis)?

From the Guidelines

Apixaban dosing should be reduced in patients with severe renal impairment, with a recommended dose of 2.5 mg twice daily for patients with creatinine clearance 15-29 mL/min. For patients with end-stage renal disease (creatinine clearance less than 15 mL/min) or on dialysis, a dose of 2.5 mg twice daily is also recommended, although clinical data in this population is limited 1. No dose adjustment is needed for mild to moderate renal impairment (creatinine clearance 30 mL/min or higher) unless other dose-reduction criteria are present. These adjustments are necessary because apixaban is partially eliminated by the kidneys (approximately 27%), and impaired renal function leads to increased drug exposure and potentially higher bleeding risk 1. When assessing renal function, the Cockcroft-Gault formula using actual body weight is recommended for calculating creatinine clearance 1. Regular monitoring of renal function is important, especially in elderly patients or those with conditions that might affect kidney function, as declining renal function may necessitate dose adjustments during treatment. Key considerations include:

• Renal function assessment using the Cockcroft-Gault formula
• Dose reduction for severe renal impairment
• Regular monitoring of renal function
• Potential for increased bleeding risk with impaired renal function It is essential to weigh the benefits and risks of apixaban use in patients with renal impairment, considering the limited clinical data available for this population 1.

From the FDA Drug Label

Apixaban is eliminated in both urine and feces. Renal excretion accounts for about 27% of total clearance. Systemic exposure to apixaban administered as a single 5 mg dose in ESRD subjects dosed immediately after the completion of a 4-hour hemodialysis session (post-dialysis) is 36% higher when compared to subjects with normal renal function No dose adjustment is recommended for nonvalvular atrial fibrillation patients unless at least 2 of the following patient characteristics (age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1. 5 mg/dL) are present.

Dosing in Impaired Renal Function:

• Impaired renal function affects the dosing of apixaban, as renal excretion accounts for about 27% of total clearance.
• In patients with end-stage renal disease (ESRD) on hemodialysis, systemic exposure to apixaban is higher compared to those with normal renal function.
• Dose adjustment is recommended for nonvalvular atrial fibrillation patients with impaired renal function if at least 2 of the following characteristics are present: age ≥ 80 years, body weight ≤ 60 kg, or serum creatinine ≥ 1.5 mg/dL 2.

From the Research

Apixaban Dosing and Renal Function

• Impaired renal function can affect the dosing of apixaban, as it is partially renally excreted 3.
• Patients with mild renal impairment (creatinine clearance of 50 to 80 ml/min) have a lower risk of bleeding with apixaban compared to conventional anticoagulants 4.
• In patients with moderate to severe renal impairment (creatinine clearance <50 ml/min), the risk of bleeding with apixaban is similar to that of conventional anticoagulants 4.
• The efficacy of apixaban in preventing stroke or systemic embolism is not affected by renal function, and it reduces the rate of major bleeding events across all ranges of estimated glomerular filtration rates (eGFRs) 3.

Dose Adjustment Criteria

• Apixaban dose adjustment criteria are based on age, weight, and serum creatinine in non-valvular atrial fibrillation (NVAF), but there are no recommended adjustment criteria for venous thromboembolism (VTE) 5.
• Pharmacokinetic studies have shown increased apixaban exposure in patients with advanced renal impairment, but clinical data suggest that there is no reduction in apixaban safety or efficacy in these patients 5.
• Apixaban-calibrated anti-Xa assays may be useful in certain circumstances, such as in patients with renal insufficiency, to guide therapeutic decision making 6.

Clinical Implications

• Renal impairment is associated with an increased risk of cardiovascular events and bleeding in patients with atrial fibrillation, but apixaban treatment reduces the rate of stroke, death, and major bleeding regardless of renal function 3, 7.
• Apixaban is effective in preventing stroke in patients with moderate chronic kidney disease, with a significant reduction in primary events compared to aspirin 7.
• The use of apixaban in patients with renal impairment requires careful consideration of the potential risks and benefits, and close monitoring of renal function and bleeding risk is recommended 4, 3.